Clinical Guidance

The variant is associated with a less severe phenotype than the other FGF3 pathogenic variants .

• Microtia was not observed in eight of 11 individuals homozygous for p.Arg95Trp; in contrast, none of the persons reported with other pathogenic variants had normal-appearing external ears.

• Inner ear structures were identified in seven of 20 individuals homozygous for p.Arg95Trp; in contrast, persons reported with other pathogenic variants had either no inner ear components or primitive vesicle-like structures.

Source: GeneReviews — "Congenital Deafness with Labyrinthine Aplasia, Microtia, and Microdontia"

Diagnostic Criteria

Suggestive Findings

The diagnosis of congenital deafness with labyrinthine aplasia, microtia, and microdontia (LAMM syndrome) should be suspected in individuals with the following:

• Profound congenital sensorineural deafness

• Severe inner ear anomalies diagnosed by CT scan or MRI of the inner ear. The most common inner ear anomaly is complete labyrinthine aplasia with no recognizable structure in the inner ear (also referred to as Michel aplasia).

• Microtia with shortening of the upper part of the auricles (also referred to as type I microtia)

• Microdontia (small teeth) with widely spaced teeth

Some individuals may also show gross motor developmental delay during infancy (presumably due to the absence of vestibular system) accompanied by additional features that include:

Source: GeneReviews — "Congenital Deafness with Labyrinthine Aplasia, Microtia, and Microdontia"

Differential Diagnosis

Table 2.

Other Genes of Interest in the Differential Diagnosis of LAMM Syndrome

Gene(s) | DiffDx Disorder | MOI | Clinical Features of DiffDx Disorder

Overlapping w/LAMM syndrome | Distinguishing from LAMM syndrome

FGF10

FGFR2

FGFR3

| Lacrimo-auriculo-dento-digital (LADD) syndrome (OMIM 149730) | AD | • Hearing loss

• Dental anomalies

| • Aplasia, atresia, or hypoplasia of the lacrimal salivary systems

• Cup-shaped ears

• Digital (particularly thumb) anomalies

EYA1

SIX1 | Branchiootorenal spectrum disorder1 | AD | Hearing loss | • Branchial fistulae cysts

• Renal malformations

KMT2D

KDM6A

| Kabuki syndrome | ADXL | • Hearing loss

Management Guidelines

Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with congenital deafness with labyrinthine aplasia, microtia, and microdontia (LAMM syndrome), the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended. Table 3. Recommended Evaluations Following Initial Diagnosis in Individuals with Congenital Deafness with Labyrinthine Aplasia, Microtia, and Microdontia

Source: GeneReviews — "Congenital Deafness with Labyrinthine Aplasia, Microtia, and Microdontia"

Clinical Guidance

Noise exposure is a well-recognized environmental cause of hearing loss. Since this risk can be minimized by avoidance, individuals with LAMM syndrome and a residual cochlea should be counseled appropriately. Because of the high risk for disorientation when submerged in water, swimming needs to be undertaken with caution.

Source: GeneReviews — "Congenital Deafness with Labyrinthine Aplasia, Microtia, and Microdontia"

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Source: GeneReviews — "Congenital Deafness with Labyrinthine Aplasia, Microtia, and Microdontia"

Surveillance Guidelines

Table 4.

Recommended Surveillance for Individuals with Deafness with Congenital Labyrinthine Aplasia, Microtia, and Microdontia

System/Concern | Evaluation | Frequency

Deafness

| ENT eval | Annually

Strabismus

| Ophthalmologic eval

Dental

| Dental eval | As neeeded

Yearly evaluations by the multidisciplinary team mentioned in is appropriate.

Source: GeneReviews — "Congenital Deafness with Labyrinthine Aplasia, Microtia, and Microdontia"